Search

The VALHUDES protocol was established to evaluate clinical accuracy of human papillomavirus (HPV) assays to detect cervical precancer on first-void urine (FVU) and vaginal self-samples versus matched clinician-collected cervical samples (CCSs). Here we evaluated clinical performance of Alinity m HR HPV assay in a colposcopy referral population. Home-collected FVU (Colli-Pee FV 5020) 1 day before colposcopy (n = 492), at-clinic collected dry vaginal self-samples [multi-Collect Swab (mC; n = 493), followed by Evalyn Brush (EB; n = 233) or Qvintip (QT; n = 260)] and matched CCSs, were available for the study. Sensitivity to detect cervical intraepithelial neoplasia grade 2 or higher (CIN2 + ) of Alinity testing on FVU (ratio, 0.94; 95% CI, 0.85-1.03), mC (ratio, 1.00; 95% CI, 0.94-1.06), and EB/QT (ratio, 0.92; 95% CI, 0.85-1.00) was not different to CCSs. Specificity on FVU was similar to CCS (ratio, 1.02; 95% CI, 0.95-1.10), whereas specificity on mC was lower (ratio, 0.83; 95% CI, 0.76-0.90), but on EB/QT was higher (ratio, 1.08; 95% CI, 1.01-1.15) than on CCS. Accuracy on EB (sensitivity ratio, 0.96; 95% CI, 0.87-1.05; specificity ratio, 1.18; 95% CI, 1.06-1.31) was slightly better than on QT (sensitivity ratio, 0.88; 95% CI, 0.75-1.03; specificity ratio, 1.00; 95% CI, 0.92-1.09). In conclusion, clinical sensitivity of Alinity assay on all self-sample types was similar to cervical specimens. Adjustment of signal thresholds improved assay's accuracy to detect CIN2 + in all self-sample types., (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The accuracy of high-risk human papillomavirus testing with the Xpert HPV assay on vaginal self-samples was compared with clinician-taken samples within the VALidation of HUman papillomavirus assays and collection DEvices for Self-samples and urine samples (VALHUDES) framework. Five-hundred and twenty-three women were recruited in five Belgian colposcopy clinics, of whom 483 (median age, 40 years; interquartile range, 31 to 49 years) were included in the main analysis (226 collected with Evalyn Brush and 257 collected with Qvintip). Cervical samples were collected with Cervex-Brush. Colposcopy and histology outcomes were considered as the reference standard. The Xpert HPV assay had similar accuracy for cervical intraepithelial neoplasia ≥2 on self-collected versus clinician-collected samples [relative sensitivity, 0.96 (95% CI, 0.91-1.02); and relative specificity, 0.96 (95% CI, 0.89-1.04)]. The relative accuracy slightly differed by vaginal collection device [sensitivity ratios of 0.98 (95% CI, 0.90-1.06) and 0.94 (95% CI, 0.87-1.02) for Evalyn and Qvintip, respectively; specificity ratios of 1.06 (95% CI, 0.95-1.19) and 0.88 (95% CI, 0.80-0.98) for Evalyn and Qvintip, respectively]. No difference in cycle threshold values was observed between vaginal and cervical samples. In conclusion, the sensitivity of Xpert HPV assay for cervical intraepithelial neoplasia ≥2 on vaginal self-samples was similar to that of cervical specimens. The clinical specificity was lower than on clinician-collected samples when self-samples were taken with Qvintip., (Copyright © 2023 Association for Molecular Pathology and American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: In this study, we evaluated accuracy of HPV testing on self-samples versus clinician-taken samples through the VALHUDES protocol. VALHUDES was designed as a diagnostic test accuracy study, where women referred to colposcopy collected self-samples followed by clinician-taken cervical samples., Methods: Four hundred eighty-five women recruited in five colposcopy clinics (median age = 40 years; IQR, 31-49) with valid results for all specimens were included in the main analysis: 230 vaginal self-samples were collected with Evalyn Brush and 255 with Qvintip. Cervical samples were taken by the gynecologist with the Cervex-Brush. HPV testing was performed with BD Onclarity HPV assay (Onclarity). Colposcopy and histology were used as the reference standard for accuracy estimation., Results: The sensitivity for CIN2+ on vaginal self-samples overall was not different from cervical samples (ratio = 0.96; 95% CI, 0.90-1.03), whereas specificity was significantly higher (ratio = 1.09; 95% CI, 1.02-1.16). However, the relative accuracy (self- vs. clinician sampling) differed by vaginal collection device: relative sensitivity and specificity ratios of 1.00 (95% CI, 0.94-1.06) and 1.15 (95% CI, 1.05-1.25), respectively for Evalyn-Brush; 0.91 (95% CI, 0.79-1.04) and 1.03 (95% CI, 0.95-1.13), respectively for Qvintip., Conclusions: Clinical accuracy of BD Onclarity HPV assay on vaginal self-samples was not different from cervical samples., Impact: VALHUDES study showed that HPV testing with Onclarity HPV on vaginal self-samples is similarly sensitive compared with cervical specimens. However, differences in accuracy by self-sampling devices, although not significant, were noted. Onclarity HPV testing on vaginal self-samples following validated collection and handling procedures may be used in primary cervical cancer screening., (©2022 American Association for Cancer Research.)

This European consensus statement on essential colposcopy provides standards for the general colposcopist seeing women referred for colposcopy with an abnormal cervical screening test (including cytology and HPV tests) or with a clinically suspicious cervix. The article gives guidance regarding the aims and conduct of colposcopy. Recommendations are provided on colposcopy technique, the management of common colposcopy issues, treatment and follow-up of after treatment of CIN or early stage cervical. Colposcopists should make an informed decision on the management of each individual that is referred and organize appropriate follow-up. Cervical cancer is still a major health issue and the quality of care can only improve if there is a structured guidance for women with an abnormal smear or suspicious cervix., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020. Published by Elsevier B.V.)

Background: Human papillomavirus (HPV) infects and propagates in the cervical mucosal epithelium. Hence, in addition to assessing systemic immunity, the accurate measurement of cervical immunity is important to evaluate local immune responses to HPV infection and vaccination. This review discusses studies that investigated the presence of infection and vaccine-induced HPV-specific antibodies in cervicovaginal secretions (CVS)., Methods: We searched the two main health sciences databases, PubMed and the ISI Web of Science, from the earliest dates available to March 2019. From the eligible publications, information was extracted regarding: (i) study design, (ii) the reported HPV-specific antibody concentrations in CVS (and the associated serum levels, when provided), (iii) the CVS collection method, and (iv) the immunoassays used., Results: The systematic search and selection process yielded 44 articles. The evidence of HPV-specific antibodies in CVS after natural infection (26/44) and HPV vaccination (18/44) is discussed. Many studies indicate that HPV-specific antibody detection in CVS is variable but feasible with a variety of collection methods and immunoassays. Most CVS samples were collected by cervicovaginal washing or wicks, and antibody presence was mostly determined by VLP-based ELISAs. The moderate to strong correlation between vaccine-induced antibody levels in serum and in CVS indicates that HPV vaccines generate antibodies that transudate through the cervical mucosal epithelium., Conclusion: Although HPV-specific antibodies have lower titres in CVS than in serum samples, studies have shown that their detection in CVS is feasible. Nevertheless, the high variability of published observations and the lack of a strictly uniform, well-validated method for the collection, isolation and quantification of antibodies indicates a need for specific methods to improve and standardize the detection of HPV-specific antibodies in CVS., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Back Ground: Systematic reviews have concluded that hrHPV DNA testing using target-amplification tests is as accurate on vaginal self-samples as on clinician-taken specimens for the detection of cervical precancer. However, insufficient evidence is available for specific HPV assay/self-sample device combinations., Objectives: The VALHUDES protocol is designed as a diagnostic test accuracy study that aims to compare the clinical sensitivity and specificity of particular hrHPV assay(s) on vaginal self-samples and first-void-urine, collected in agreement with standardized protocols, with hrHPV testing on matched clinician-taken samples., Study Design: Five hundred enrolled women referred to a colposcopy clinic are invited to collect a first-void urine sample and one or more vaginal self-samples with particular devices before collection of a cervical sample by a clinician. Sample sets are subsequently analysed in a laboratory accredited for HPV testing. Disease verification for all enrolled patients is provided by colposcopy combined with histological assessment of biopsies., Results: A first VALHUDES study has started in Belgium in December 2017 with enrolment from four colposcopy centres. The following assays are foreseen to be evaluated: RealTime High Risk HPV assay (Abbott), cobas-4800 and -6800 (Roche), Onclarity (BD), Xpert HPV (Cepheid) and Anyplex II HPV HR (Seegene)., Conclusion: Given empirical evidence that the relative accuracy of HPV-testing on self- vs clinician-samples is robust across clinical settings, the VALHUDES protocol offers a framework for validation of HPV assay/self-sample device combinations that can be translated to a primary screening setting., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Due to cervical cancer screening the number of squamous cancer have declined. The number of adenocarcinomas (ADCs) does appear to be rising. ADCs are often missed and human papillomavirus (HPV) testing could be helpful in detecting these abnormalities earlier., Case: A 36-year-old woman, who had a normal smear three years earlier, had a pap smear with atypical glandular cells. The L1 HPV test showed that there was no HPV infection. Other HPV tests which looked at E6 and E7 showed an infection with HPV 16. Due to unknown reasons, no action was taken regarding the atypical glandular cells. Two years later the patient was diagnosed with a FIGO Stage IVb ADC of the cervix. The L1 HPV test was still negative and the E6/E7 HPV test was still positive. Despite several multiple treatment modalities she succumbed of her disease two years later leaving behind a young family., Conclusion: HPV test looking only at L1 can give false negative results if the virus is integrated in the human genome.

Cervical cancer can and should be a historical disease. The reality, however, is that every year more than half a million women are diagnosed with cervical cancer and a quarter of a million die of this disease. The causal factor for cervical cancer is a persistent HPV infection and therefore a vaccine was developed: prophylactic HPV vaccination will reduce cervical cancer by 70%. Screening based on cytology will miss more than 40% of the abnormalities. The introduction of vaccination should lead to the reintroduction of cervical cancer screening based on HPV detection. Primary HPV screening followed by cytology will detect almost all abnormalities. Not all HPV tests, however, are the same! Clinicians are generally not aware that there is a huge difference among HPV tests. If a low grade lesion progresses to a high grade or invasive cancer, their HPV is likely to integrate. During integration L1 expression can be lost, but E6/E7 expression will always remain present. If the viral HPV is completely integrated then a L1 test looking for only L1 expression will miss this (pre)cancer, while the E6/E7 test will not miss it. HPV tests used in cervical cancer screening should be based on the early (E) and the late (L) genes in order not to miss the abnormality., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The prevalence of penile cancer varies between 1.5 (industrialized countries) and 4.5 per 100,000 men (non-industrialized countries). Predominant histological subtype is squamous cell carcinoma (SCC). Human papillomavirus (HPV) is found in 40-46% of cases: penile cancer is considered to behave as vulvar cancer. Non HPV related risk factors are lack of circumcision, phimosis, chronic inflammation, and smoking. The role of lichen sclerosus (LS) is unclear. Clinical diagnosis is difficult and treatment often mutilating. Preventive measures can be taken since the risk factors are known: the use of the prophylactic HPV vaccines may contribute. We measured the prevalence of HPV and LS in penile cancer in Belgium., Materials and Methods: We found 76 samples of penile lesions in the archives of the departments of Histology of four university hospitals in Belgium. Real-time PCR of type-specific HPV DNA was performed targeting 18 HPV types., Principal Results: Patients with penile intraepithelial neoplasia (PeIN) were 56.1 years of age: patients with invasive penile cancer (IPC) 68.5 (p=0.009). Fifty-five samples (55/76) were adequate for HPV targeting. Overall HPV DNA was 70.9%: 89.5% in samples of PeIN (n=19) and 61.1% in samples of IPC (n=36). Invasive penile cancer samples were less likely to be HPV infected (p=0.028). HPV 16 was most prevalent: 48.3%: 20% PeIN, and 28.3% IPC. HPV DNA of the types, included in the prophylactic vaccines, was found in 33% of PeIN and 31.7% of IPC samples. Thrice, low risk HPV (lrHPV) types 6 (1 IPC) and 11 (1 PeIN, 1 IPC) were solely present. There was no difference in the presence of LS between HPV positive and HPV negative samples (p=0.944)., Conclusions: Prevalence of HPV DNA in penile lesions in Belgium is high. However, the prophylactic vaccines may contribute to primary prevention of only a subset of cases. The role of LS remains unclear., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Persistent infection with high-risk Human papillomavirus (hr-HPV 16, 18, 31, 33, and 45) is the main risk factor for developing malignant genital lesions. Screening methods and follow-up schedules for cervical cancer are well known. A golden standard to screen and monitor men does not exist yet, because HPV-related, life threatening malignancies in men are rare. The importance of male HPV screening lies mainly in HPV vaccination. Young females are the target group for HPV, but men are considered to be the reservoir for HPV and to have a role in the perpetuation of the infection in the general population. We looked at the usefulness of urine as a tool for HPV screening. Pubmed was searched with the words ''HPV'', ''Urine,'' and ''HPV-DNA''. The chance of finding HPV-DNA in urine is higher in men with lesions in the urethra than outside the urethra, and in women with abnormal cervical cytology. In general, the results of testing urine for HPV-DNA are better for women than for men, probably because of the anatomical position of the urethra to the vagina, vulva, and cervix. In both genders, urine HPV prevalence is higher in HIV pos patients and in high-risk populations. Urine, to screen asymptomatic low-risk-profile (wo)men seems less useful because their urine samples are often inadequate. If urine proves to be the best medium to screen, a low-risk population remains controversial.

Purpose: To collect information about HPV in men and the (possible) correlation with HVP infection in women., Methods: Review of the literature., Results: An overview of HPV-related penile and anal malignancies in men and the risk factors of acquiring HPV., Conclusion: In men HPV is also partially responsible for anogenital malignancies. Although the prevalence of HPV-related malignancies in men is much lower than in women, it is useful to gain more knowlege. Especially knowing if men are really the HPV reservoir and transmitters for women can make a difference in deciding whether men should also be screened for HPV and if they are good candidates for vaccination.

Aim: To investigate whether urine is a good medium for screening and whether there is a correlation between the amount of extracted DNA and human papillomavirus (HPV)-positivity., Methods: In the present study, 30 first-voided urine (FVU) specimens and 20 urethroglandular swabs using cervex-brushes from male partners of HPV-positive patients, and 31 FVU specimens and 100 liquid-based cervix cytology leftovers sampled with cervix-brushes from HPV-positive women were examined for the presence of beta-globin. Oncogenic HPV were detected using type-specific PCR., Results: beta-globin was found in all the brushed samples, whereas it was found in only 68.9% of the FVU specimens. HPV-PCR was positive in 60.0% of the male brushes, in 29% of the female brushes and in 0% of the male FVU specimens. DNA concentration was, respectively, 0.9998 ng/microL, 37.0598 ng/microL and 0.0207 ng/microL., Conclusion: Urine is not a good tool for HPV detection, probably because the low DNA concentration reflects a low amount of collected cells. beta-globin is measurable in FVU by real time quantitative PCR, but the DNA concentration is lower compared to brush sampling for both genders. beta-globin-positivity of urethral and cervical swabs is 100%, showing a higher mean concentration of DNA, leading to a higher detection rate of HPV. This is the first article linking DNA-concentration to the presence of HPV.

Human papillomavirus (HPV) infection is the most common sexually transmitted disease, with more than 80% of the population infected at some time in their life. In rare cases, this infection may lead to cervical cancer. Virtually all squamous cell carcinomas and the overwhelming majority of adenocarcinomas of the cervix are HPV positive. HPV integration in the genome will lead to inactivation of the p53 pathway and the Rb pathway. Integration is essential for the onset of cervical carcinogenesis, but is probably not sufficient for progression to invasive cervical cancers. It is likely that several cofactors, such as environmental, viral and host-related factors, are necessary for the development of cervical cancer. There are several similarities and differences between the two major histological types. This article will address the role of HPV in cervical carcinogenesis as well as the molecular biology involved in the process.

Persistent infection with one of the oncogenic human papillomavirus (HPV) types is a necessity for the development of cervical cancer. By HPV vaccination, cervical cancer could become a very rare disease. Two types of HPV vaccines can be distinguished: (i) therapeutic vaccines which induce cellular immunity targeted against epithelial cells infected with HPV and (ii) prophylactic vaccines inducing virus-neutralizing antibodies protecting against new but not against established infections. At present, several vaccines have been developed and tested in clinical trials. The vaccines are generally well tolerated and highly immunogenic. The current clinical data indicate that prophylactic vaccines are very effective against new persistent infections and the development of cervical intraepithelial lesions. The protection is type specific. However, the follow-up of the vaccination trials is still short. The effect of HPV vaccines on future cancer incidence will only be known after decades of follow-up. This article will address the status of recently terminated phase II and currently running phase III trials with prophylactic HPV vaccines.

Worldwide there is a strong relation between the presence of human papillomavirus (HPV) and the development of cervical cancer. This study investigated the prevalence and genotype of HPV in women with normal smears, women with premalignant lesions and women with cervical cancer in Antwerp, Belgium. Type-specific polymerase chain reaction (PCR) for HPV types 16 and 18 and general primer PCR (GP5+/6+) was performed on DNA extracted from paraffin-embedded tissue from women with lesions or fresh material from controls. HPV was detected in 11% of controls, 61% of women with atypia, 77% of women with CIN lesions and 88% of women with cervical carcinoma (chi2 trend, 273, p<0.001). The odds ratio for high-risk HPV types was 9.3 for atypia (95%CI. 4.3-19.8), 33.6 for CIN lesions (95%CI, 19.3-58.6) and 78.8 for cervical cancer (95%CI, 39.2-158.3). In total, 19 different HPV genotypes were detected, including five low risk HPV types. Seven of the 14 high-risk HPV types were detected in cervical cancer patients. Based on our study it is suggested that a prophylactic vaccine based on a cocktail of a limited number of high-risk HPV types should be considered in order to protect most women from developing cervical cancer.